The Newborn Kidney in Health & Disease pps

Victor S. Doctor, MD Victor S. Doctor, MD 10 10 th th PNSP Annual Convention PNSP Annual Convention November 17, 2005 November 17, 2005 SERUM URINE GFR = 110 ml/min Na – 140 meq/liter = 150 liters in 24 hours (21,000 meq Na) 20,790 or 99% Reabsorbed *Neonates Filter only One-twenty fifth of Volume as that of the adults 210 meq lost in 1% URINE 2 liter urine output (105 meq Na/liter Less filtered Less to absorb Less filtered Less to absorb = = Less work Less work (Slightly used!) (Slightly used!) = = More energy available More energy available for growth for growth Reason for less work Reason for less work = = Too young Too young = = Matures in 8 weeks Matures in 8 weeks or more or more Tubule Tubule Epithelium Epithelium Blood Blood Na Na Na Na Na 65% Na 65% Na 25% Na 25% Na 5% Na 5% Na 1-3% Na 1-3% Proximal Proximal TAL TAL DCT DCT CCT CCT 99% Absorption 1% Na Excreted = Enzymes for ABSORPTION less abundant to perform work (absorption) = More Na excreted (lost) Less capacity to reabsorb Na and fluids Less capacity to reabsorb Na and fluids - Disadvantage? - Disadvantage? NO! NO! There is less to reabsorb anyway. There is less to reabsorb anyway. (due to filtration) (due to filtration) WHAT / WHEN : WHAT / WHEN : Increase in transporter Increase in transporter activity (absorption) activity (absorption) Neonates Neonates - - low glucocorticoid levels low glucocorticoid levels - - low thyroid hormone levels low thyroid hormone levels Adults Adults - - higher levels of higher levels of glucocorticoid & glucocorticoid & thyroid hormone thyroid hormone - - more transporter enzymes more transporter enzymes found in tubules found in tubules - - GFR increase GFR increase - - more tubular solutes to more tubular solutes to absorb absorb Water Reabsorption Water Reabsorption : Fractional reabsorption : Fractional reabsorption - - the same as in adults but the same as in adults but water channels are less water channels are less (Aquaporins) (Aquaporins) Glucocorticoids: Glucocorticoids: 1. increase Na+ transporters for reabsorption 1. increase Na+ transporters for reabsorption 2. increase Aquaporin activities 2. increase Aquaporin activities Studies show that – Studies show that – Prenatal Glucocorticoid administration Prenatal Glucocorticoid administration increases Na+ transporter and aquaporin increases Na+ transporter and aquaporin maturation and activities. maturation and activities. Collecting Duct: Collecting Duct: Final sodium modulation segment to Final sodium modulation segment to maintain homeostasis maintain homeostasis Less Na channels are found in neonates Less Na channels are found in neonates * Tendency to lose more Na thru the urine * Tendency to lose more Na thru the urine Acid-Base Balance Acid-Base Balance 80% HCO3 absorbed at proximal tubule 80% HCO3 absorbed at proximal tubule Neonates: HCO3 reabsorption is lower by 1/3 Neonates: HCO3 reabsorption is lower by 1/3 that of adults that of adults = low HCO3 transporter activity = low HCO3 transporter activity = all transporter steps for reabsorption of = all transporter steps for reabsorption of HCO3 are underdeveloped in the HCO3 are underdeveloped in the neonates neonates H H Na Na [...]... High intake and protein metabolism acid 2-3 meq/k/day Aggressive Total Parenteral Nutrition (TPN) may cause acidosis Large amount of Arginine in TPN for premature infants can result in metabolic acidosis (Arginine is a source of HCl) Why is neonate not acidotic if excretion is decreased? Mother’s milk contains base equivalents to maintain acid/base balance Premature milk contains higher proteins,...There is clear evidence that glucocorticoids stimulate development of HCO3 transport (Pregnant rabbits injected glucocorticoids prior to delivery = their neonates have proximal tubule HCO3 transport rate comparable to that of the adults Amonia Genesis NH3 H+ GLUTAMINE NH3 NH4 NH3 catches H+ NH4 In Acidosis amonioagenesis increase 10x in adults * Neonates CANNOT Normal adult protein metabolism... regimen) Evidence: 1 Rats treated with dexamethasone prenatally developed HPN as they become adults 2 Their kidneys developed glomerulo SCLEROSIS Glucocorticoids may initially show beneficial effects thru neonatal interventions for specific situations BUT may have ADVERSE effects in later life MAN GETS INTO TROUBLE BY RE-DIRECTING NATURES FORCES ... Handling by Healthy and Sick Neonates K = 100-150 meq/liter intracellular For: = Cellular functions, e.g Muscle contractility = Component of new cells for growth and cellular division Adult = 0 K+ balance Neonates = (+) K+ balance to incorporate into new cells for somatic growth K+ like Fe+ = actively transported via placenta even in maternal K+ deficiency Neonatal Hyper K+ = failure of Na K pump in. .. Hyper K+ = failure of Na K pump in very premature neonates = corrected by prenatal steroid treatment stabilizing cell membrane Filtered K+ - almost entirely absorbed at proxime tubule (in normal newborn) Na K Cl – tubular absorption process is related to common transporters Tendency to retain K or Decreased K+ excretion due to relative immaturity of CCD transporter which improves with maturation Role . amount of Arginine in TPN for premature Large amount of Arginine in TPN for premature infants can result in metabolic acidosis infants can result in metabolic acidosis (Arginine is a source. Mother’s milk contains base equivalents to maintain acid/base balance. maintain acid/base balance. Premature milk contains higher proteins, Premature milk contains higher proteins, sodium, potassium. administration increases Na+ transporter and aquaporin increases Na+ transporter and aquaporin maturation and activities. maturation and activities. Collecting Duct: Collecting Duct: Final